Purpose: To characterize the clinical phenotype of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) optic neuritis. Design: Observational case series. Methods: SETTING: Multicenter. PATIENT/STUDY POPULATION: Subjects meeting inclusion criteria: (1) history of optic neuritis; (2) seropositivity (MOG-IgG binding index > 2.5); 87 MOG-IgG-seropositive patients with optic neuritis were included (Mayo Clinic, 76; other medical centers, 11). MOG-IgG was detected using full-length MOG-transfected live HEK293 cells in a clinically validated flow cytometry assay. MAIN OUTCOME MEASURES: Clinical and radiologic characteristics and visual outcomes. Results: Fifty-seven percent were female and median age at onset was 31 (range 2–79) years. Median number of optic neuritis attacks was 3 (range 1–8), median follow-up 2.9 years (range 0.5–24 years), and annualized relapse rate 0.8. Average visual acuity (VA) at nadir of worst attack was count fingers. Average final VA was 20/30; for 5 patients (6%) it was ≤20/200 in either eye. Optic disc edema and pain each occurred in 86% of patients. Magnetic resonance imaging showed perineural enhancement in 50% and longitudinally extensive involvement in 80%. Twenty-six patients (30%) had recurrent optic neuritis without other neurologic symptoms, 10 (12%) had single optic neuritis, 14 (16%) had chronic relapsing inflammatory optic neuropathy, and 36 (41%) had optic neuritis with other neurologic symptoms (most neuromyelitis optica spectrum disorder–like phenotype or acute disseminated encephalomyelitis). Only 1 patient was diagnosed with MS (MOG-IgG-binding index 2.8; normal range ≤ 2.5). Persistent MOG-IgG seropositivity occurred in 61 of 62 (98%). A total of 61% received long-term immunosuppressant therapy. Conclusions: Manifestations of MOG-IgG-positive optic neuritis are diverse. Despite recurrent attacks with severe vision loss, the majority of patients have significant recovery and retain functional vision long-term.
Bibliographical noteFunding Information:
Funding/Support: This work was supported by the Department of Laboratory Medicine and Pathology and the Center for MS and Autoimmune Neurology, Mayo Clinic , Rochester, Minnesota, and in part by an unrestricted grant to the Department of Ophthalmology by Research to Prevent Blindness, Inc, New York, New York. J. L. Bennett was supported by grants from the National Institutes of Health (EY022936, UM1AI110498) and the National Multiple Sclerosis Society . Financial Disclosures: Brian G. Weinshenker receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of neuromyelitis optica (NMO)-IgG as a diagnostic test for NMO and related disorders; serves as a member of an adjudication committee for clinical trials in NMO being conducted by VielaBio and Alexion pharmaceutical companies; is a consultant for Caladrius Biosciences, Brainstorm Therapeutics, and Riovant Sciences regarding potential clinical trials for NMO; and serves as a member of a data safety monitoring committee for clinical trials conducted by Novartis. Andrew McKeon has a patent pending for GFAP and MAP1B as markers of neurologic autoimmunity and paraneoplastic disorders; consulted for Grifols, Medimmune, and Euroimmun; and received research support from Medimmune and Euroimmun but has not received personal compensation. Vanda A. Lennon receives royalties for technology relating to aquaporin 4 (AQP4) antibodies for diagnosis of NMO and its spectrum disorders; and is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker. B. Mark Keegan receives research funding from Biogen for the ARISE trial, and publishing royalties for Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases. Orhun H. Kantarci receives grant support from Biogen. Michael S. Lee is a named inventor on filed patents on potentiating botulinum toxin, and received research support from Quark. Jeffrey L. Bennett serves as a consultant for MedImmune, EMD Serono, Abbvie, Genentech, and Genzyme; receives license and royalties for a patent re: Compositions and Methods for the Treatment of Neuromyelitis Optica (Aquaporumab); and receives research support from Mallinckrodt Pharmaceuticals and EMD Serono. Victoria S. Pelak receives royalties from Up-to-Date. Dean M. Wingerchuk has received personal compensation as a consultant for Caladrius Biosciences, Inc, Brainstorm Cell Therapeutics, ONO Pharmaceuticals, and Celgene and as a member of an adjudication committee for a clinical trial from MedImmune; and as co–editor-in-chief of The Neurologist ; and has received clinical research/grant support paid to Mayo Clinic from Alexion Pharmaceuticals, Inc, Terumo BCT, Inc, and the Guthy-Jackson Charitable Foundation. Sean J. Pittock is a named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker; consulted for Alexion and Medimmune; and received research support from Grifols, Medimmune, and Alexion; all compensation for consulting activities is paid directly to Mayo Clinic. The following authors have no financial disclosures: John J. Chen, Eoin P. Flanagan, Jiraporn Jitprapaikulsan, James P. Fryer, Jacqueline A. Leavitt, W. Oliver Tobin, Collin M. McClelland, Yanjun Chen, Gregory VanStavern, Ore-Ofe O. Adesina, Marie D. Acierno, Paul W. Brazis, and Jessica Sagen. All authors attest that they meet the current ICMJE criteria for authorship. Dr. Lopez Chiriboga, Tillema, and Eggenberger have no disclosures. Dr. Lucchinetti has a patent related to NMO-IgG and research support from Novartis and Biogen, but this did not impact this study.